Evaluating the Safety and Efficacy of Decitabine in the Treatment of XMEN Patients

Fudan University

Status and phase: Not yet enrolling; Phase 4

Conditions: MAGT1 Deficiency

Treatments: Drug: Decitabine

Study type: Interventional

Funder types: Other

Identifiers

NCT07555405

IIT2026008

Details and patient eligibility

About

This is a single-arm, open-label, single-center, exploratory clinical trial evaluating the safety and efficacy of decitabine in male patients aged 1 month to 18 years with X-linked magnesium transporter 1 (MAGT1) deficiency. Eligible patients have a confirmed MAGT1 gene mutation leading to XMEN disease ( X-linked MAGT1 deficiency with increased susceptibility to Epstein-Barr virus (EBV) infection and N-linked glycosylation defect). The study will assess changes in liver function, immune function, and NKG2D expression, as well as adverse events, over four treatment cycles and the follow-up period.

Full description

XMEN disease is a rare X-linked primary immunodeficiency caused by loss-of-function mutations in MAGT1, leading to chronic Epstein-Barr virus (EBV) infection, liver dysfunction, and reduced NKG2D expression on lymphocytes. TUSC3 shares functional redundancy with MAGT1 but is epigenetically silenced in immune and liver tissues. Decitabine, a DNA methyltransferase inhibitor, can reactivate TUSC3 expression.

This single-arm, open-label, single-center study will enroll six male participants aged 1 month to 18 years with genetically confirmed MAGT1 mutation and a clinically diagnosis of XMEN disease. Eligible participants will receive decitabine intravenously at 20 mg/m² once daily for five consecutive days every four weeks, for a total of four cycles. Safety and efficacy will be evaluated by monitoring NKG2D expression, liver enzymes levels, EBV viral load, lymphocyte function, TUSC3 expression, and adverse events. Participants will be followed for 180 days after the last dose.

Enrollment: 6 estimated patients

Sex: Male

Ages: 1 month to 18 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Male participants aged 1 month to 18 years old.
2. Confirmed MAGT1 gene mutation by genetic testing.
3. Clinical manifestations consistent with XMEN disease, including liver dysfunction and/or EBV infection.
4. Reduced lymphocyte NKG2D expression.
5. Vital signs within normal range at screening.
6. Expected survival ≥ 6 months.
7. Able to comply with study procedures.
8. Guardian and participant provide written informed consent.

Exclusion criteria

1. Hypersensitivity to decitabine or any excipient.
2. Hematopoietic stem cell transplantation within 1 year before enrollment.
3. Severe concurrent organ dysfunction or systemic disease.
4. Positive HBsAg, anti-HCV, syphilis, or HIV test.
5. Neurological or psychiatric disorders that impair compliance.
6. Participation in another clinical trial within 3 months.
7. Other conditions judged inappropriate by the investigator.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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6 participants in 1 patient group

Decitabine, Route of administration: Intravenous infusion

Other group

Description:

Participants receive decitabine at a dose of 20 mg/m² once daily for five consecutive days per treatment cycle. Each dose is administered as a continuous intravenous infusion over at least one hour. Each cycle consists of five doses, and a total of four cycles are planned.

Treatment:

Drug: Decitabine